Hydrophilic-hydrophobic active ingredient dual delivery system and preparation method and application thereof

Abstract

The present invention discloses a hydrophilic-hydrophobic active ingredient dual delivery system and its preparation method and application, the preparation method comprising: providing an organic phase solution containing embedded carrier particles and hydrophobic active ingredients, providing an aqueous phase solution containing hydrophilic active ingredients, and dripping the aqueous phase solution into the organic phase solution for embedding under stirring at 25-65°C; wherein the embedded carrier particles are liposomes. The hydrophilic-hydrophobic active ingredient dual delivery system can achieve the synchronous delivery of two or more hydrophilic active ingredients and hydrophobic active ingredients, which can not only effectively solve the pain points of poor stability and difficulty in transdermal penetration of hydrophilic active ingredients, but also improve the stability and formula compatibility of hydrophobic active raw materials.

Description

Technical Field

[0001] The present invention relates to the field of biochemical technology, and in particular to a hydrophilic-hydrophobic active ingredient dual delivery system and a preparation method and application thereof. Background Art

[0002] Functional active ingredients are widely used in the cosmetics, health food and other industries, but many active ingredients have problems such as instability, odor, poor compatibility, and low bioavailability, which seriously restrict their application in cosmetics and food.

[0003] Functional active ingredients can be roughly divided into hydrophilic active ingredients and hydrophobic active ingredients. Generally speaking, they need to be delivered in a stable state through different encapsulation techniques. This not only increases the cost in front-end encapsulation technology development, but also increases the complexity of product formula design and development during the application process.

[0004] Therefore, it is urgent to develop a system that can simultaneously deliver hydrophilic active ingredients and hydrophobic active ingredients to solve the above problems. Summary of the invention

[0005] The purpose of the present invention is to solve the problem that hydrophilic active ingredients and hydrophobic active ingredients usually need to be delivered in a stable state through different encapsulation techniques, which increases development costs and reduces compatibility, thereby providing a hydrophilic-hydrophobic active ingredient dual delivery system and a preparation method and application thereof. The hydrophilic-hydrophobic active ingredient dual delivery system can achieve the simultaneous delivery of two or more hydrophilic active ingredients and hydrophobic active ingredients, which can not only effectively solve the pain points of poor stability and difficulty in skin penetration of hydrophilic active ingredients, but also improve the stability and formula compatibility of hydrophobic active ingredients.

[0006] In order to achieve the above-mentioned object, the first aspect of the present invention provides a preparation method of a hydrophilic-hydrophobic active ingredient dual delivery system, the preparation method comprising: providing an organic phase solution containing embedded carrier particles and hydrophobic active ingredients, providing an aqueous phase solution containing hydrophilic active ingredients, and dripping the organic phase solution into the aqueous phase solution under stirring at 25-65°C for embedding; wherein,

[0007] The embedded carrier particles are liposomes.

[0008] The second aspect of the present invention provides a hydrophilic-hydrophobic active ingredient dual delivery system prepared by the above-mentioned preparation method.

[0009] The third aspect of the present invention provides a hydrophilic-hydrophobic active ingredient dual delivery system, which comprises an embedded carrier particle and an active component loaded on the embedded carrier particle; wherein:

[0010] The embedded carrier particles are liposomes;

[0011] The active components include hydrophobic active ingredients and hydrophilic active ingredients.

[0012] The fourth aspect of the present invention provides an application of the above-mentioned hydrophilic-hydrophobic active ingredient dual delivery system in cosmetics.

[0013] In the above technical scheme, the present invention loads the hydrophobic active ingredients on the embedding carrier ions to form an organic phase, and then uses the organic phase to embed the hydrophilic active ingredients. Since the hydrophilic active ingredients mainly exist inside the phospholipid bilayer vesicles and the inner water phase, and the hydrophobic active ingredients mainly exist between the phospholipid bilayers, the hydrophilic-hydrophobic active ingredient dual delivery system of the present invention can achieve the synchronous stable embedding delivery of hydrophilic-hydrophobic active ingredients.

[0014] The hydrophilic-hydrophobic active ingredient dual delivery system of the present invention forms a multi-component functional complex through weak interactions (such as van der Waals forces, hydrogen bonding, ionic electrostatic effects or hydrophobic effects, etc.) between the hydrophilic active ingredients, the hydrophobic active ingredients and the embedded carrier particles, and improves the stability of these systems through further encapsulation and strengthening. It not only effectively solves the pain points of poor stability and difficulty in skin penetration of hydrophilic active ingredients, but also improves the stability and formula compatibility of hydrophobic active raw materials.

[0015] At the same time, the preparation method of the hydrophilic-hydrophobic active ingredient dual delivery system of the present invention is simple and easy to operate, can be mass-produced, saves time and material costs, and provides more possibilities for the design, development, innovation and upgrading of cosmetics.

[0016] Other features and advantages of the present invention will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the following specific embodiments, they are used to explain the present invention but do not constitute a limitation of the present invention. In the accompanying drawings:

[0018] Figure 1 Schematic diagram of the preparation of the hydrophilic-hydrophobic active ingredient dual delivery system of the present invention;

[0019] Figure 2 3 is a scanning electron microscope image of the hydrophilic-hydrophobic active ingredient dual delivery system prepared in Examples 2, 3 and 5 of the present invention. DETAILED DESCRIPTION

[0020] The specific embodiments of the present invention are described in detail below. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0021] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0022] The first aspect of the present invention provides a method for preparing a hydrophilic-hydrophobic active ingredient dual delivery system, the preparation method comprising: providing an organic phase solution containing embedded carrier particles and hydrophobic active ingredients, providing an aqueous phase solution containing hydrophilic active ingredients, and dripping the organic phase solution into the aqueous phase solution under stirring at 25-65°C for embedding; wherein,

[0023] The embedded carrier particles are liposomes.

[0024] The preparation method of the hydrophilic-hydrophobic active ingredient dual delivery system of the present invention is simple and easy to operate, can be mass-produced, saves time and material costs, and provides more possibilities for the design, development, innovation and upgrading of cosmetics.

[0025] In a preferred embodiment of the present invention, the method for providing an organic phase solution comprises: dissolving the embedded carrier particles and the hydrophobic active ingredient in an organic solvent to obtain an organic phase solution containing the embedded carrier particles and the hydrophobic active ingredient.

[0026] In a preferred embodiment of the present invention, the method for providing an aqueous phase solution comprises: dissolving a hydrophilic active ingredient in water to obtain an aqueous phase solution containing the hydrophilic active ingredient, wherein the water is preferably deionized water.

[0027] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the preparation method further comprises: adding a strengthening agent to the aqueous phase solution.

[0028] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the enhancer is a polymer enhancer and / or an inorganic particle enhancer.

[0029] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the polymer enhancer is selected from one or more of chitosan, chitin, cellulose, protein, nucleic acid and starch.

[0030] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the inorganic particle strengthener is selected from one or more of silicon dioxide, titanium dioxide, calcium carbonate, calcium silicate and calcium phosphate.

[0031] In a preferred embodiment of the present invention, the particle size of the inorganic particle strengthening agent is 5 nm-100 μm, preferably 10 nm-50 μm, and more preferably 10 nm-10 μm.

[0032] In a preferred embodiment of the present invention, in order to remove the organic solvent in the hydrophilic-hydrophobic active ingredient dual delivery system and enable the hydrophilic-hydrophobic active ingredient dual delivery system to be better used, the preparation method further includes a drying process.

[0033] In a preferred embodiment of the present invention, the drying method is selected from one or more of rotary evaporation, freeze drying, spray drying, vacuum drying, double cone drying, heating drying and room temperature drying.

[0034] In a preferred embodiment of the present invention, in order to improve the water solubility, dispersibility and compatibility of the hydrophilic-hydrophobic active ingredient dual delivery system, a drying protectant needs to be added during freeze drying, and the drying protectant accounts for 5%-95% of the solid mass.

[0035] In a preferred embodiment of the present invention, the desiccation protective agent is an oligosaccharide, which can be selected from one or more of sucrose, fructose, trehalose, mannitol, lactose, glucose and maltose.

[0036] In a preferred embodiment of the present invention, in order to enable the prepared hydrophilic-hydrophobic active ingredient dual delivery system to be well applied in corresponding fields, the preparation method further includes a particle size reduction process.

[0037] In a preferred embodiment of the present invention, the particle size reduction process may use common particle size reduction processes such as ultrasonic dispersion method and homogenization method.

[0038] In a preferred embodiment of the present invention, in order to achieve a better encapsulation effect for the hydrophilic-hydrophobic active ingredient dual delivery system, the mass ratio of the liposome to the hydrophobic active ingredient is 1:0.001-1, preferably 1:0.01-0.2, and more preferably 1:0.02-0.1.

[0039] In a preferred embodiment of the present invention, in order to achieve a better encapsulation effect for the hydrophilic-hydrophobic active ingredient dual delivery system, the liposome is selected from one or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, cholesterol and PEGylated phospholipids.

[0040] In a preferred embodiment of the present invention, when the liposome is a composite liposome, the preparation method of the composite liposome is a commonly used method, for example, a thin film dispersion method, an organic solvent injection method (the organic solvent can be commonly used organic solvents such as ethanol, acetone, petroleum ether, dichloromethane and tetrahydrofuran), an ultrasonic dispersion method, a homogenization method, and an extrusion method.

[0041] In a preferred embodiment of the present invention, the hydrophobic active ingredient mainly refers to oil-soluble or lipophilic functional active raw materials used in cosmetics and other products, for example, it can be selected from one or more of phloretin, ceramide, vitamin E, vitamin A alcohol, astaxanthin, curcumin, docosahexaenoic acid, DHA, lutein, carotene and glabridin.

[0042] In a preferred embodiment of the present invention, in order to better dissolve the lipid components and the hydrophobic active substances, the solvent of the organic phase solution is selected from one or more of ethanol, acetone, petroleum ether, dichloromethane and tetrahydrofuran.

[0043] In a preferred embodiment of the present invention, in order to enable the prepared hydrophilic-hydrophobic active ingredient dual delivery system to be well applied in the corresponding fields, the particle size range of the embedded carrier particles is 10nm-1mm, preferably 50nm-500μm, more preferably 100nm-100μm, and further preferably 200nm-10μm.

[0044] In a preferred embodiment of the present invention, the hydrophilic active ingredient mainly refers to water-soluble or hydrophilic functional active raw materials used in cosmetics and other products, for example, it can be selected from one or more of blue copper peptides, glutathione, active polypeptides, niacinamide, ethylbisiminomethylguaiacol manganese chloride (EUK134), vitamin C, vitamin B3 and vitamin B5.

[0045] In a preferred embodiment of the present invention, in order to achieve a better encapsulation effect for the hydrophilic-hydrophobic active ingredient dual delivery system, the mass ratio of the liposome to the hydrophilic active ingredient is 1:0.001-2, preferably 1:0.01-1, and more preferably 1:0.02-0.2.

[0046] The second aspect of the present invention provides a hydrophilic-hydrophobic active ingredient dual delivery system prepared by the above-mentioned preparation method.

[0047] The third aspect of the present invention provides a hydrophilic-hydrophobic active ingredient dual delivery system, which comprises an embedded carrier particle and an active component loaded on the embedded carrier particle; wherein:

[0048] The embedded carrier particles are liposomes;

[0049] The active components include hydrophobic active ingredients and hydrophilic active ingredients.

[0050] The hydrophilic-hydrophobic active ingredient dual delivery system provided by the present invention is achieved by loading the hydrophobic active ingredient on an embedding carrier ion to form an organic phase, and then using the organic phase to embed the hydrophilic active ingredient. Since the hydrophilic active ingredient mainly exists inside the phospholipid bilayer vesicle and the inner water phase, while the hydrophobic active ingredient mainly exists between the phospholipid bilayers, the synchronous stable embedding delivery of the hydrophilic-hydrophobic active ingredients is achieved.

[0051] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the hydrophilic-hydrophobic active ingredient dual delivery system further contains a strengthener.

[0052] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the enhancer is a polymer enhancer and / or an inorganic particle enhancer.

[0053] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the polymer enhancer is selected from one or more of chitosan, chitin, cellulose, protein, nucleic acid and starch.

[0054] In a preferred embodiment of the present invention, in order to improve the stability of the hydrophilic-hydrophobic active ingredient dual delivery system, the solid particle strengthener is selected from one or more of silicon dioxide, titanium dioxide, calcium silicate, calcium carbonate and calcium phosphate.

[0055] In a preferred embodiment of the present invention, in order to ensure the stability and compatibility of the composite liposome, the particle size of the inorganic particle strengthening agent is 5 nm-100 μm, preferably 10 nm-50 μm, and more preferably 10 nm-10 μm.

[0056] In a preferred embodiment of the present invention, in order to make the prepared hydrophilic-hydrophobic active ingredient dual delivery system better used in the corresponding fields, the particle size range of the embedded carrier particles is 10nm-1mm, preferably 50nm-500μm, more preferably 100nm-100μm, and further preferably 200nm-10μm.

[0057] In a preferred embodiment of the present invention, in order to achieve a better encapsulation effect for the hydrophilic-hydrophobic active ingredient dual delivery system, the liposome is selected from one or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, cholesterol and PEGylated phospholipids.

[0058] In a preferred embodiment of the present invention, the hydrophobic active ingredient mainly refers to oil-soluble or lipophilic functional active raw materials used in cosmetics and other products, for example, one or more of phloretin, ceramide, vitamin E, vitamin A alcohol, astaxanthin, curcumin, docosahexaenoic acid, DHA, lutein, carotene and glabridin can be selected.

[0059] In a preferred embodiment of the present invention, the hydrophilic active ingredient mainly refers to water-soluble or hydrophilic functional active raw materials used in cosmetics and other products, for example, it can be selected from one or more of blue copper peptides, glutathione, active polypeptides, niacinamide, ethylbisiminomethylguaiacol manganese chloride (EUK134), vitamin C, vitamin B3 and vitamin B5.

[0060] In a preferred embodiment of the present invention, in order to achieve a better encapsulation effect for the hydrophilic-hydrophobic active ingredient dual delivery system, the mass ratio of the liposome, the hydrophilic active ingredient and the hydrophobic active ingredient is 1:0.001-2:0.001-1, preferably 1:0.01-1:0.01-0.2, and more preferably 1:0.02-0.2:0.02-0.1.

[0061] In a preferred embodiment of the present invention, the hydrophilic-hydrophobic active ingredient dual delivery system has a final product form of powder, solid particles, semi-solid paste or dispersion, etc., according to actual application requirements.

[0062] The fourth aspect of the present invention provides an application of the above-mentioned hydrophilic-hydrophobic active ingredient dual delivery system in cosmetics.

[0063] The present invention will be described in detail below through examples, but the protection scope of the present invention is not limited thereto. In the following examples, the drugs and medicaments are all conventional commercial products.

[0064] Example 1

[0065] Preparation of nicotinamide-phloretin dual delivery system

[0066] (1) Preparation of organic phase solution: Weigh 200 mg of soybean lecithin PC90, 16.65 mg of cholesterol, and 2 mg of phloretin, respectively, and dissolve them in 2 mL of anhydrous ethanol to prepare phloretin-soybean lecithin PC90 / cholesterol-ethanol solution;

[0067] (2) Thin film dispersion: The phloretin-soybean phospholipid PC90 / cholesterol-ethanol solution in step (1) was dried by rotary evaporation under stirring at 60° C. to form a thin film on the wall of a round-bottom flask;

[0068] (3) Preparation of aqueous solution: Weigh 80 mg of nicotinamide into a 50 mL round-bottom flask and add 10 mL of deionized water to dissolve it to prepare a nicotinamide aqueous solution;

[0069] (4) Preparation of dual delivery system: The film in step (2) was hydrated with the nicotinamide aqueous solution in step (3). After hydration, the film was sheared and homogenized for 15 min using a shear homogenizer to ensure uniform dispersion. Then, 0.5 g of trehalose was added and stirred to dissolve and disperse evenly. Finally, freeze-dried for 24 h to obtain a nicotinamide-phloretin dual delivery system, denoted as B1.

[0070] Example 2

[0071] Preparation of blue copper peptide-vitamin E dual delivery system

[0072] (1) Preparation of organic phase solution: Weigh 75 mg of soybean lecithin PC90, 12.5 mg of cholesterol, and 5.0 mg of vitamin E respectively, and dissolve them in 3 mL of anhydrous ethanol to prepare a vitamin E-soybean lecithin PC90 / cholesterol-ethanol solution;

[0073] (2) Preparation of aqueous solution: Weigh 50 mg of blue copper peptide into a 10 mL glass bottle, add 10 mL of deionized water to dissolve, and prepare a blue copper peptide aqueous solution;

[0074] (3) Preparation of dual delivery system: Slowly drip the vitamin E-soy lecithin PC90 / cholesterol-ethanol solution in step (1) into the blue copper peptide aqueous solution in step (2) while stirring in an oil bath at 40°C, and continue stirring for 15 min. Rotary evaporate at 50°C for 40 min to remove ethanol, add 0.25 g trehalose and 0.25 g mannitol, and disperse by ultrasound for 10 min to dissolve and disperse evenly. Freeze-dry the dispersion for 24 h to obtain the blue copper peptide-vitamin E dual delivery system, denoted as B2.

[0075] Example 3

[0076] Preparation of blue copper peptide-vitamin E-silicon dioxide dual delivery system

[0077] (1) Preparation of organic phase solution: Weigh 75 mg of soybean lecithin PC90, 12.5 mg of cholesterol, and 5.0 mg of vitamin E respectively, and dissolve them in 3 mL of anhydrous ethanol to prepare a vitamin E-soybean lecithin PC90 / cholesterol-ethanol solution;

[0078] (2) Preparation of aqueous solution: Weigh 50 mg of blue copper peptide into a 10 mL glass bottle, add 10 mL of deionized water to dissolve, and prepare a blue copper peptide aqueous solution;

[0079] (3) Adding inorganic particle strengthener: Weigh 50 mg of nano-silicon dioxide and disperse it in the blue copper peptide aqueous solution in step (2), and ultrasonicate for 10 minutes to disperse evenly to obtain a blue copper peptide-silicon dioxide aqueous dispersion;

[0080] (4) Preparation of dual delivery system: Slowly drop the vitamin E-soy lecithin PC90 / cholesterol-ethanol solution in step (1) into the blue copper peptide-silica aqueous dispersion in step (3) under stirring in an oil bath at 40°C, and continue stirring for 15 minutes. Rotary evaporate at 50°C for 40 minutes to remove ethanol, add 0.25 g trehalose and 0.25 g mannitol, and disperse by ultrasound for 10 minutes to dissolve and disperse evenly. Freeze-dry the dispersion for 24 hours to obtain a blue copper peptide-vitamin E-silica dual delivery system, which is recorded as B3.

[0081] Example 4

[0082] Preparation of EUK134-ceramide-methylcellulose dual delivery system

[0083] (1) Preparation of organic phase solution: Weigh 200 mg of hydrogenated soybean lecithin, 30 mg of cholesterol, and 5.0 mg of ceramide respectively, and dissolve them in 5 mL of tetrahydrofuran to prepare a ceramide-hydrogenated soybean lecithin / cholesterol-tetrahydrofuran solution;

[0084] (2) Preparation of aqueous solution: weigh 30 mg of EUK134 into a 20 mL glass bottle, add 10 mL of deionized water to dissolve, and prepare EUK134 aqueous solution;

[0085] (3) Adding polymer enhancer: Weigh 20 mg of methyl cellulose and disperse it in the EUK134 aqueous solution in step (2), and ultrasonicate for 10 min to disperse evenly to obtain a EUK134-methyl cellulose aqueous phase solution;

[0086] (4) Preparation of dual delivery system: Slowly drip the ceramide-hydrogenated soybean lecithin / cholesterol-tetrahydrofuran solution in step (1) into the EUK134-methylcellulose aqueous solution in step (3) under stirring in a 40°C oil bath, and continue stirring for 15 minutes. Rotary evaporate at 40°C for 30 minutes to remove tetrahydrofuran, add 0.25 g of trehalose and 0.25 g of mannitol, and disperse by ultrasound for 10 minutes to dissolve and disperse evenly. The dispersion was freeze-dried for 24 hours to obtain the EUK134-ceramide-methylcellulose dual delivery system, which was recorded as B4.

[0087] Example 5

[0088] Preparation of blue copper peptide / nicotinamide-phloretin / ceramide-silk fibroin multiple delivery system

[0089] (1) Preparation of organic phase solution: Weigh 250 mg of hydrogenated soybean lecithin, 250 mg of egg yolk lecithin, 60 mg of cholesterol, 5 mg of phloretin, and 5.0 mg of ceramide respectively, and dissolve them in 10 mL of tetrahydrofuran to prepare phloretin / ceramide-hydrogenated soybean lecithin / egg yolk lecithin-tetrahydrofuran solution;

[0090] (2) Preparation of aqueous solution: Weigh 50 mg of blue copper peptide, 100 mg of nicotinamide, and 50 mg of silk fibroin, respectively, dissolve them in 20 mL of deionized water, stir for 20 min, and disperse them evenly to obtain a blue copper peptide / nicotinamide-silk fibroin aqueous solution;

[0091] (3) Preparation of dual delivery system: Slowly drip the phloretin / ceramide-hydrogenated soybean lecithin / egg yolk lecithin-tetrahydrofuran solution in step (1) into the blue copper peptide / nicotinamide-silk fibroin aqueous solution in step (2) under stirring in a 40°C oil bath, and continue stirring for 15 minutes. Rotary evaporate at 40°C for 30 minutes to remove tetrahydrofuran, add 0.8 g of maltodextrin, and disperse by ultrasonic for 10 minutes to dissolve and disperse evenly. The dispersion was freeze-dried for 24 hours to obtain a blue copper peptide / nicotinamide-phloretin / ceramide-silk fibroin multiple delivery system, denoted as B5.

[0092] Test Example 1

[0093] The embedding rate of hydrophilic active ingredients in the hydrophilic-hydrophobic active ingredient dual delivery systems B1-B5 prepared in Examples 1-5 was determined in the following steps. The results are shown in Table 1.

[0094] (1) Weigh 1 g of the hydrophilic-hydrophobic active ingredient dual delivery system B1-B5 powder prepared in Examples 1-5, dissolve in deionized water, disperse evenly by ultrasonication, and then determine the total content of the hydrophilic active ingredient by HPLC;

[0095] (2) Weigh 1 g of each of the hydrophilic-hydrophobic active ingredient dual delivery systems B1-B5 prepared in Examples 1-5, dissolve them in deionized water, and then separate the free hydrophilic active ingredients and the hydrophilic active ingredients encapsulated by the liposomes (supernatant components) by ultra-high-speed centrifugation (500,000 g). Then, determine the content of the free hydrophilic active ingredients (in the lower water layer) by HPLC.

[0096] (3) Calculate the encapsulation rate of hydrophilic active substances.

[0097] Table 1

[0098]

[0099] It can be seen from the data in Table 1 that the embedding rate of the hydrophilic active substance in the hydrophilic-hydrophobic active ingredient dual delivery system prepared by the present invention is greater than 50%, and after adding the enhancer, the embedding rate of the hydrophilic active substance is increased to more than 80%, which is significantly better than the ordinary liposome embedding system. This proves that the hydrophilic-hydrophobic active ingredient dual delivery system of the present invention can improve the embedding rate of water-soluble active substances, and also proves that the embedding enhancer can effectively enhance the embedding rate of water-soluble active substances, so as to facilitate the utilization and absorption of water-soluble active substances.

[0100] Test Example 2

[0101] The embedding efficiency of hydrophobic active ingredients in the hydrophilic-hydrophobic active ingredient dual delivery systems B1-B5 prepared in Examples 1-5 was determined in the following steps. The results are shown in Table 2.

[0102] (1) Weigh 1 g of the hydrophilic-hydrophobic active ingredient dual delivery system B1-B5 powder prepared in Examples 1-5, dissolve in deionized water, disperse evenly by ultrasonication, and then determine the total content of the hydrophobic active ingredient by HPLC;

[0103] (2) Weigh 1 g of the hydrophilic-hydrophobic active ingredient dual delivery system B1-B5 powder prepared in Examples 1-5, respectively, dissolve in deionized water, and then separate the free hydrophobic active ingredient and the hydrophobic active ingredient encapsulated by the liposome (present in the liposome in the supernatant) by low-speed centrifugation (3000 rpm), and then determine the content of the encapsulated hydrophobic active ingredient in the supernatant by HPLC;

[0104] (3) Calculate the encapsulation rate of the hydrophobic active ingredient.

[0105] Table 2

[0106]

[0107] It can be seen from the data in Table 2 that the encapsulation rate of the hydrophobic active ingredient in the hydrophilic-hydrophobic active ingredient dual delivery system prepared by the present invention is basically above 90%, indicating that the hydrophobic active ingredient is well encapsulated, which is beneficial to the transportation and utilization of the hydrophobic active substance.

[0108] Test Example 3

[0109] The dispersibility index (PDI) of the hydrophilic-hydrophobic active ingredient dual delivery systems B1-B5 prepared in Examples 1-5 was measured. The dispersibility index (PDI) is shown in Table 3.

[0110] Table 3

[0111]

[0112] From the data in Table 3, it can be seen that the particle size of the liposomes (embedded carrier particles) in the simple composite liposome systems of the nicotinamide-phloretin dual delivery preparation B1 prepared in Example 1 and the blue copper peptide-vitamin E dual delivery preparation B2 prepared in Example 2 is basically less than 200 nm, and the monodispersity is better. The hydrophilic-hydrophobic active ingredient dual delivery systems B3-B5 prepared in Examples 3-5 added enhancers. Although the particle size of the composite liposomes increased, they still maintained relatively good dispersibility.

[0113] Test Example 4

[0114] The blue copper peptide series samples B2, B3 and B5 prepared in Examples 2, 3 and 5 were selected for SEM analysis. Figure 2 .

[0115] from Figure 2 It can be seen that for a relatively simple encapsulation system such as the blue copper peptide-vitamin E dual delivery preparation B2 prepared in Example 2, the liposomes are basically spherical, and the particle size of the liposomes is also relatively small, basically below 200 nm, while the blue copper peptide-vitamin E-silicon dioxide dual delivery preparation B3 prepared in Example 3 adds silicon dioxide or the blue copper peptide / nicotinamide-phloretin / ceramide-silk protein multiple delivery preparation prepared in Example 5 adds silk protein composite liposomes, the particle size is larger, and there are some irregularities after drying, and the results are basically consistent with the PDI test results.

[0116] Test Example 5

[0117] The blue copper peptide series samples B2, B3 and B5 prepared in Examples 2, 3 and 5 were selected to determine the stability of the blue copper peptide encapsulated delivery preparations under accelerated experimental conditions at 50°C. The results are shown in Table 4.

[0118] The blue copper peptide or the blue copper peptide series samples B2, B3 and B5 prepared in Examples 2, 3 and 5 were prepared into aqueous solutions with a concentration of about 2 mg / ml and tested and evaluated at 37°C.

[0119] Table 4

[0120]

[0121] It can be seen from Table 4 that the stability of the blue copper peptide is significantly improved after the hydrophilic-hydrophobic active ingredient dual delivery system of the present invention is embedded in the composite liposome; the data on the 30th day of the accelerated experiment show that the retention rate of the blue copper peptide in the embedded delivery preparation is increased by 20%, or even higher, and the addition of the embedding enhancer in Example 3 and Example 5 is beneficial to improve the stability of the blue copper peptide.

[0122] Application Example 1

[0123] The application of the B2 copper peptide-vitamin E dual delivery preparation and the B3 copper peptide-vitamin E-silicon dioxide dual delivery preparation prepared in Examples 2 and 3 in the "soothing repair essence". The model formula of the essence was designed, and the compatibility and transdermal absorption of the copper peptide series samples B2 and B3 prepared in Examples 2 and 3 were evaluated.

[0124] The control sample formula is a formula with blue copper peptide added directly, and the concentration of blue copper peptide remains the same. The brief process of formula preparation is as follows:

[0125] (1) Weigh the raw materials of phase A in sequence, heat at 40°C and stir evenly;

[0126] (2) After stirring and cooling, add phase B and stir evenly, then discharge the material to obtain the soothing and repairing essence;

[0127] Among them, for the above three formulation systems, the specific formulas of phase A and phase B are shown in Tables 5 to 7.

[0128] Table 5 Blue Copper Peptide-Essence Model Formula

[0129]

[0130] Table 6 Blue copper peptide-vitamin E dual delivery preparation-essence model formula

[0131]

[0132] Table 7 Blue copper peptide-vitamin E-silicon dioxide dual delivery formulation-essence model formula

[0133]

[0134] For the above three formula systems, a comparison of the transdermal efficacy of blue copper peptide was conducted. The evaluation method was based on the “In vitro test method for skin absorption of chemicals”. The results are shown in Table 8.

[0135] Table 8

[0136]

[0137] From the transdermal efficacy evaluation results in Table 8, the transdermal absorption of the blue copper peptide of the blue copper peptide series samples B2 and B3 of the present invention is about 3 times that of the single blue copper peptide, which is significantly better than the single blue copper peptide. This shows that the use of composite liposomes to embed the blue copper peptide in the present invention can promote the transdermal absorption of the blue copper peptide, and also proves that the stability of the embedded blue copper peptide is significantly improved, which is also conducive to transdermal absorption.

[0138] In summary, the integrated encapsulation and delivery preparation of the hydrophilic active ingredient and the hydrophobic active ingredient of the present invention not only improves the stability and transdermal absorbability of the sensitive hydrophilic active ingredient, but also improves the stability and compatibility of the hydrophobic active. At the same time, by adding an encapsulation enhancer, the stability and encapsulation rate of the liposome are further improved, which is better than the ordinary liposome delivery system. In addition, the integrated encapsulation and delivery preparation enhances the efficacy synergy of active ingredients with different functions, and also reduces the pain points of compatibility in product formula design, providing strong technical support and guarantee for the product innovation and upgrading of functional cosmetics.

[0139] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0140] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0141] In addition, various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A method for preparing a hydrophilic-hydrophobic active ingredient dual delivery system, characterized in that: The preparation method comprises: providing an organic phase solution containing embedded carrier particles and hydrophobic active ingredients, providing an aqueous phase solution containing hydrophilic active ingredients, and dripping the organic phase solution into the aqueous phase solution under stirring at 25-65° C. for embedding; wherein, The embedded carrier particles are liposomes; The preparation method further comprises: adding a strengthening agent to the aqueous phase solution; The reinforcing agent is a polymer reinforcing agent and / or an inorganic particle reinforcing agent; The polymer reinforcing agent is selected from methylcellulose and / or silk fibroin; The inorganic particle strengthening agent is selected from silicon dioxide; The hydrophobic active ingredient is selected from one or more of phloretin, ceramide and vitamin E; The hydrophilic active ingredient is selected from one or more of blue copper peptide, nicotinamide and ethylbisiminomethylguaiacol manganese chloride.

2. The preparation method according to claim 1, characterized in that: The particle size of the inorganic particle strengthening agent is 5nm-100μm.

3. The preparation method according to claim 1, characterized in that: The particle size of the inorganic particle strengthening agent is 10nm-50μm.

4. The preparation method according to claim 1, characterized in that: The particle size of the inorganic particle strengthening agent is 10nm-10μm.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The mass ratio of the liposome to the hydrophobic active ingredient is 1:0.001-1.

6. The preparation method according to any one of claims 1 to 4, characterized in that: The mass ratio of the liposome to the hydrophobic active ingredient is 1:0.01-0.

2.

7. The preparation method according to any one of claims 1 to 4, characterized in that: The mass ratio of the liposome to the hydrophobic active ingredient is 1:0.02-0.

1.

8. The preparation method according to claim 1, characterized in that: The material of the liposome is selected from two or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, cholesterol and PEGylated phospholipids.

9. The preparation method according to claim 1, characterized in that: The solvent of the organic phase solution is selected from one or more of ethanol, acetone, petroleum ether, dichloromethane and tetrahydrofuran.

10. The preparation method according to claim 1, characterized in that: The particle size of the embedded carrier particles ranges from 10 nm to 1 mm.

11. The preparation method according to claim 1, characterized in that: The particle size of the embedded carrier particles ranges from 50nm to 500μm.

12. The preparation method according to claim 1, characterized in that: The particle size of the embedded carrier particles ranges from 100 nm to 100 μm.

13. The preparation method according to claim 1, characterized in that: The particle size of the embedded carrier particles ranges from 200 nm to 10 μm.

14. The preparation method according to claim 1, characterized in that: The mass ratio of the liposome to the hydrophilic active ingredient is 1:0.001-2.

15. The preparation method according to claim 1, characterized in that: The mass ratio of the liposome to the hydrophilic active ingredient is 1:0.01-1.

16. The preparation method according to claim 1, characterized in that: The mass ratio of the liposome to the hydrophilic active ingredient is 1:0.02-0.

2.

17. A hydrophilic-hydrophobic active ingredient dual delivery system prepared by the preparation method according to any one of claims 1 to 16.

18. A hydrophilic-hydrophobic active ingredient dual delivery system, characterized in that: The hydrophilic-hydrophobic active ingredient dual delivery system comprises embedded carrier particles and active components loaded on the embedded carrier particles; wherein, The embedded carrier particles are liposomes; The active components are hydrophobic active ingredients and hydrophilic active ingredients; The hydrophilic-hydrophobic active ingredient dual delivery system further comprises an enhancer; The reinforcing agent is a polymer reinforcing agent and / or an inorganic particle reinforcing agent; The polymer reinforcing agent is selected from methylcellulose and / or silk fibroin; The inorganic particle strengthening agent is selected from silicon dioxide; The hydrophobic active ingredient is selected from one or more of phloretin, ceramide and vitamin E; The hydrophilic active ingredient is selected from one or more of blue copper peptide, nicotinamide and ethylbisiminomethylguaiacol manganese chloride.

19. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The particle size of the inorganic particle strengthening agent is 5nm-100μm.

20. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The particle size of the inorganic particle strengthening agent is 10nm-50μm.

21. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The particle size of the inorganic particle strengthening agent is 10nm-10μm.

22. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The material of the liposome is selected from two or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, cholesterol and PEGylated phospholipids.

23. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The mass ratio of the liposome, the hydrophilic active ingredient and the hydrophobic active ingredient is 1:0.001-2:0.001-1.

24. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The mass ratio of the liposome, the hydrophilic active ingredient and the hydrophobic active ingredient is 1:0.01-1:0.01-0.

2.

25. The hydrophilic-hydrophobic active ingredient dual delivery system according to claim 18, characterized in that: The mass ratio of the liposome, the hydrophilic active ingredient and the hydrophobic active ingredient is 1:0.02-0.2:0.02-0.

1.

26. Use of the hydrophilic-hydrophobic active ingredient dual delivery system according to claim 17 or the hydrophilic-hydrophobic active ingredient dual delivery system according to any one of claims 18 to 25 in the preparation of cosmetics.

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